A Raleigh, North Carolina population of Drosophila melanogaster was sampled to determine the frequency of null alleles at 25 allozyme loci. Nulls were found at 13 of 20 autosomal loci with a weighted mean frequency of 0.0025, with a range from 0.00 to 0.01. No nulls were found at five X-chromosome loci. We tentatively suggest that enzyme nulls may be part of the genetic variation contributing to the inbreeding depression observed when chromosomes taken from nature are made homozygous.